Stable isotope analyzer

ABSTRACT

A stable isotope analyzer is concentration calibrated by measuring relative proportions of isotopes in a measurement gas. The measurement gas is a component of a gaseous mixture consisting of the measurement gas and one other gas or a mixture of gases containing none of the measurement gas. First, a mixture is produced with a relatively high concentration of the measurement gas and known isotope proportions. The concentration of the measurement gas in the other gas is determined and the isotope proportion is measured to determine a point on a calibration curve (measured isotope proportion values vs. measured concentration values). At least one further point on the calibration curve is determined by diluting the measurement gas in the mixture by introducing a gas or gaseous mixture containing no measurement gas. The reduced concentration is determined and the isotope proportion measured to determine another point on the calibration curve. The steps of reducing the measurement gas concentration in the gaseous mixture, measuring the measurement gas concentration, and measuring the isotope proportion are preferably repeated a plurality of times to plot the calibration curve more accurately.

BACKGROUND OF THE INVENTION

The invention relates to a method of concentration calibration of astable isotope analyzer and to a stable isotope analyzer with means forconcentration calibration.

In many fields of science (archeology, biology, geology, medicine,physiology, pharmacology) growing significance is attributed to thedetermination of isotope proportions. This applies primarily to themeasurement of the 13CO₂ /12CO₂ ratio in the CO₂ of the respiratory gas,which provides valuable information with respect to diagnostic queries.Stable isotope analyzers permit the performance of measurements of theisotope proportion, for example determination of the selective isotopeproportion (*A_(x),B_(y)) in a measurement gas (A_(x),B_(y)) or thedetermination of the ratio at which the isotope proportions exists. Whenmeasuring the 13C/12C ratio, specifically in a respiratory gas stableisotope diagnostic, specification of the so-called Delta-value has foundacceptance, where a measured relative value is related to a standardratio.

With the aid of non-disperse infra-red spectroscopy, a method is knownfor selective determination of an isotope proportion of a measurementgas (EP-A-584 897). The appliance described by way of exemplaryembodiment serves for measuring the 13CO₂ /12CO₂ ratio.

It comprises two ray paths or analyzers, one of which serves formeasuring the 13CO₂ -proportion and the other for measuring the 12CO₂-proportion.

When taking isotope proportion measurements, it has come to light thatthe result depends upon the concentration in which the measurement gasis present in another gas (for example CO₂ in an inert gas) or a mixtureof gas (for example CO₂ in air). In order to obtain measuring resultsnot subject to said dependence, it is necessary to undertake aconcentration calibration, prior to taking measurements.

In the appliance according to EP-A-584 897, calibration of the analyzeris done with the aid of calibration cells, which can--inserted behindthe measuring cells--be pivoted into the respective ray path. Thecalibration cells are filled with a mixture of an inert gas and theisotope-free measurement gas proportion belonging to the respective pathof rays. CO₂ -free air flows through the measuring cells duringcalibration.

In order to perform a concentration-calibration with an appliance ofthis type, a plurality of calibration cells must first be made availablewith different concentrations of isotope-free portions of themeasurement gas in an inert gas. These must be pivoted, successively,into the ray paths and, after completion of taking the concentrationmeasurement, must again be tilted out. From the plurality of theindividual concentration measurements, which are respectively requiredfor each ray path, it is possible to determine the dependence of theisotope portions measurements on the concentration in the inert gas.

The concentration calibration can also be performed without anymechanical pivoting of the appropriate calibration cells. In such case,however, one proceeds from the premise that the course of the signals issimilar to the concentration for each of the two isotope proportions,and that there will be no error or only negligible errors inestablishing the ratio.

It has be determined in actual practice that such an assumption isjustified with respect to the accuracy of the measurements that need tobe obtained. For this type of calibration, a series of gas test samplesmust be made available and successively measured, with varying andcorrespondingly closely graduated CO₂ -concentrations and a constantDelta-value.

It is the object of the present invention to significantly simplify theconcentration calibration of a stable isotope analyzer.

This object is solved according to the invention by the identifyingcharacteristics of the Patent Claims.

SUMMARY OF THE INVENTION

In accordance with one aspect of the present invention, a method forcalibration of a stable isotope analyzer for isotope proportionmeasurements in a measurement gas is provided.

In accordance with another aspect of the present invention, a stableisotope analyzer is provided. The analyzer includes first and secondmeasuring cells, a conveyor pump, and a line connection between thesecond cell and the conveyor pump.

One advantage of the present invention is that calibration of a stableisotope analyzer is achieved rapidly and accurately.

Another advantage of the present invention is that calibration isachieved with a single calibration sample of known Delta-value.

Still further advantages of the present invention will become apparentto those of ordinary skill in the art upon reading and understanding thefollowing detailed description of the preferred embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may take form in various components and arrangements ofcomponents and the various steps and arrangements of steps. The drawingsare only for purposes of illustrating a preferred embodiment and are notto be construed as limiting the invention.

FIG. 1 is a schematic diagram of a stable isotope analyzer in themeasurement phase, according to the present invention;

FIG. 2 is a schematic diagram of the stable isotope analyzer of FIG. 1with valve 11 open to admit respiratory air;

FIG. 3 is a schematic diagram of the stable isotope analyzer of FIG. 1during circulation of respiratory air; and

FIG. 4 is a schematic diagram of the stable isotope analyzer of FIG. 1with the valve positions adjusted for the short-term inflow of CO₂ -freeair.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Based on the proposed measures, it is possible to eliminate thepreparation of a plurality of test samples with varying CO₂-concentrations and constant Delta values in a gas mixture. This appliesas well with respect to the mechanical appliances by which the pluralityof test samples must be pivoted, in succession, into the two paths ofthe rays. The only requirement is that one gas mixture be prepared,having a relatively high CO₂ -concentration and a known Delta-value.This means, that the concentration of the measurement gas in the testsample should lie at the upper limit of the range in which themeasurement concentration normally lies.

If a non-disperse infra-red spectrometer is employed for performance ofthe isotope proportion measurements, having measuring cells whichfacilitate selective determination of isotope proportions, then theinstrument can also be utilized for measurement of concentrationrequired for calibration. The course of these concentration measurementsis almost identical with the course of the isotope proportionmeasurements, so that the instrument itself need undergo only minormodifications in order to be able to execute concentration calibrationsquickly, reliably and with precision. The possibility exists forautomation, so that no specially trained personnel is needed to operatethe instrument. Additional benefits and details of the invention areexplained more specifically based on the exemplary embodiments depictedin FIGS. 1 to 4.

The Figures show, in highly diagrammatic view, the gas control in aninfra-red stable isotope analyzer. The analyzer comprises two measuringcells 1 and 2, and also eight connection stubs 3 to 10 withelectro-magnetically actuable valves 11 to 18. The connection stubs endin a line 21, which communicates via line 23 by conveyor pump 24 withthe first measuring cell 1. The measuring cells 1 and 2 are connected bythe line segment 25 such that during the measurement phase the measuringgas flows successively through the measuring cells. Measuring cell 2 isconnected with line 26, via which the measuring gas flows to the outlet27, which is formed in the depicted exemplary embodiment by a3/2-way-valve 28.

Into line 21 also issues air supply line 31 with valve 32. In addition,CO₂ -free air may be supplied to line 21. To that end, line 33 isprovided with valves 35 and 36 and also with a cartridge 37 in which islocated an adsorption medium for CO₂, for example soda lime.

FIG. 1 represents the position of the valves in a measurement phase inwhich measuring gas flows in via the connection stub 4. In a respiratorygas analysis, for example, eight respiratory gas bags are connected toconnection stubs 3 to 10, which are successively connected withmeasuring cells 1 and 2. A purging period is inserted before eachmeasurement taking, during which the entire ray path is purged with air.The valves of the respiratory air bags are closed and only the "air"line 31 is open. Subsequently, the "air" line 31 is closed again andvalve 12, located in front of the to be measured respiratory air bag, isopened. Before the start of the measurement taking, during the "waitingperiod" (length approximately 30 seconds) the entire volume (lines,measuring cells) is flooded with respiratory air. Subsequent thereto,the measurement is executed under constant continued pumping. Once thebag has been measured, the instrument automatically--controlled by acomputer--switches over to the next respiratory bag and the operationcontinues.

Execution of a concentration calibration in respiratory analysis isgoing to be explained by means of FIGS. 2-4. Connected to connectionstub 3 is a respiratory air bag containing respiratory air withrelatively high CO₂ -concentration. Said test sample can, for example,be prepared in that a respiratory air bag is filled by exhalation from aperson who held his/her breath for a short period of time. Prior tocalibration, the entire volume is purged with CO₂ -free air andsubsequently valve 11 is opened. After flooding the entire volume withrespiratory air, valve 11 is closed and valve 28 brought into a positionin which the respiratory air is circulated (compare FIG. 3). For thatpurpose, line segment 41 is provided, which connects valve 28 with theinlet of conveyor pump 24. With the aid of measuring cells 1 and/or 2,the absolute CO₂ -concentration is measured during this phase and theDelta-Value ascertained. From these measurements, a point is establishedin the system of coordinates for the calibration curve (Delta Valueversus concentration). In order to determine another point of thecalibration curve, the respiratory gas which is located in the system isdiluted with CO₂ -free air, so that there is a reduction in the CO₂-concentration. FIG. 4 depicts the valve positions needed during theshort-term inflow of CO₂ -free air. Valves 35, 36 are in open position.A part of the circulated gas flows out via valve 28. Subsequently, thevalves are again positioned according to FIG. 3 and the steps"measurement of concentration" and "measurement of Delta-Value" arerepeated. This results in obtaining another point on the calibrationcurve, The desired calibration curve is obtained by means of additional,gradual dilution of gas within the system and repeatedmeasurement-taking. The degree of concentration modification is adjustedvia chronologically regulated opening of valves 35 and 36.

The represented appliance also permits calibration of the zero point. Itis the purpose of said calibration to set to "0" the measurement valueof the CO₂ -concentration, read by the instrument, when the air that istotally devoid of CO₂. For that purpose, the instrument is supplied withair via cartridge 37, containing soda lime, which chemically binds theCO₂.

When required, measurement taking is automatic and lasts until themeasured value no longer shows fluctuations. The instrument is then setto "0" per internal command.

It is fundamental, however, that the invention facilitates the executionof a concentration calibration with an only slightly modified stableisotope analyzer, which is simple, reliable and precise. Because of thepossibility of automating the measurement taking and also thecalibration course, the sequences can be regulated by computer. It isappropriate to enter the calibration curve into the memory bank so thatcomparison with the calibration curve of the Delta-values measured onadditional respiratory gas samples can likewise be automated.

The invention has been described with reference to the preferredembodiment. Obviously, modifications and alterations will occur toothers upon reading and understanding the preceding detaileddescription. It is intended that the invention be construed as includingall such modifications and alterations insofar as they come within thescope of the appended claims or the equivalents thereof.

Having thus described the preferred embodiment, the invention is nowclaimed to be:
 1. A method for concentration calibration of a stableisotope analyzer employed for isotope proportion measurements in ameasurement gas, wherein the measurement gas is a component of a gasmixture which consists of the measurement gas and an additional gas, theadditional gas being devoid of the measurement gas and the gas mixture,the method including:preparing the gas mixture by mixing the measuringgas and the additional gas, which gas mixture has a relatively highmeasurement gas concentration and known isotope proportions; determininga first point on a calibration curve of isotope proportions versusconcentration measurement values, the determining of the pointincluding:determining a first concentration of the measurement gas inthe gas mixture, and measuring a first isotope proportion in the gasmixture; determining another point on the calibration curve by:reducingthe concentration of the measurement gas in the gas mixture by supplyinga gas devoid of the measurement gas and the gas mixture, determininganother concentration of the measurement gas in the gas mixture, andmeasuring another isotope proportion in the gas mixture; repeating thesteps of reducing the concentration of the measurement gas in the gasmixture, determining another concentration of the measurement gas, andmeasuring another isotope proportion a plurality of times to produce acalibration curve.
 2. The method according to claim 1, carrying out themeasurement case concentration determining steps with a measuringinstrument which is present in the stable isotope analyzer.
 3. Themethod according to claim 1 wherein:the isotope proportions are measuredwith a non-disperse infra-red spectrometer with two measuring cells forselective determination of the isotope proportions; and the gas mixtureconcentrations are determined with at least one of the measuring cells.4. The method according to claim 3, wherein the gas mixtureconcentration is determined with a first of the measuring cells which aproportion of a predominantly occurring isotope.
 5. The method accordingto claim 3, wherein the measurement gas is circulated via the measuringcells during the calibration.
 6. The method according to claim 1,wherein the measurement gas is CO₂, wherein the steps of measuring thefirst and another isotope proportions measures absolute concentrationsof CO₂ isotopes, and further including:determining a Delta-value fromthe absolute concentrations of the CO₂ isotopes.
 7. The method accordingto claim 5, wherein the analyzer serves for performing CO₂ -isotopeproportion measurements in respiratory gas, and wherein the step ofpreparing the gas mixture with the relatively high measurement gasconcentration includes filling a respiratory bag by exhalation from aperson who has held a breath for a short period of time.
 8. A stableisotope analyzer including:a first measuring cell and a second measuringcell for execution of isotope proportion measurements, the firstmeasuring cell having a first measuring cell inlet and a first measuringcell exit, the second measuring cell having a second measuring cellinlet and a second measuring cell exit, the second measuring cell inletbeing connected with the first measuring cell exit such that the secondmeasuring cell receives a gas which has flowed through the firstmeasuring cell; a conveyor pump having an intake and a conveyor pumpexit; a first line connection between the second measuring cell exit andthe conveyor pump intake; and, a second line connection between theconveyor pump exit and the first measuring cell inlet.
 9. The analyzeraccording to claim 8, wherein a 3/2-way valve is located in the firstline connection for selectively connecting the second measuring cellexit with a gas outlet and with the conveyor pump intake.
 10. A methodfor determining isotope proportions in a measuring gas which includes afirst stable isotope and a second stable isotope, proportions of thefirst stable isotope and second stable isotope in the measuring gasvarying with a concentration of the measuring gas in a mixtureconsisting of the measuring gas and a second gas, the methodcomprising:a) introducing a calibration sample into an analyzer, thecalibration sample including the measuring gas with a known initialproportion of the first stable isotope and the second stable isotope; b)determining a concentration of the measuring gas in the calibrationsample; c) measuring a proportion of the first stable isotope relativeto the second stable isotope in the calibration sample; d) diluting thecalibration sample with a diluting gas to reduce the concentration ofthe measuring gas, the diluting gas being substantially free of themeasuring gas; e) repeating steps (b) through (d) to obtain acalibration curve of the isotope proportion versus the concentration ofthe measuring gas in the analyzer; f) purging the analyzer to remove thecalibration sample from the analyzer; g) introducing a sample to betested into the analyzer, the sample to be tested containing themeasuring gas; h) determining a concentration of the measuring gas inthe sample to be tested; i) determining the proportion of the first andstable isotopes in the sample to be tested; and, j) correcting theproportion measured for the sample with the calibration curve.
 11. Themethod according to claim 10, wherein the sample to be treated includesair exhaled from a person who has held their breath for a short periodof time and the measuring gas is carbon dioxide.
 12. The methodaccording to claim 11, wherein the diluting gas includes air from whichcarbon dioxide has been removed.
 13. A method for concentrationcalibration of a stable isotope comprising:determining a firstconcentration of a measurement gas in a gas mixture; reducing theconcentration of the measurement gas in the gas mixture by supplying agas devoid of the measurement gas and the gas mixture; determining thereduced concentration of the measurement gas in the gas mixture.
 14. Themethod as set forth in claim 13 further including:from the determinedfirst and reduced concentrations, determining a calibration curve.